金丝桃苷对大鼠脑缺血/再灌注损伤的血管保护作用:大电导Ca2+激活的K+通道的激活。

IF 3 4区 医学 Q2 NEUROSCIENCES Neural Plasticity Pub Date : 2023-08-14 eCollection Date: 2023-01-01 DOI:10.1155/2023/5545205
Wen-Ming Hong, Yue-Wu Xie, Meng-Yu Zhao, Tian-Hang Yu, Li-Na Wang, Wan-Yan Xu, Shen Gao, Hua-Bao Cai, Yan Guo, Fang Zhang
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引用次数: 0

摘要

金丝桃苷(Hyp)是一种中草药,对多种疾病有多种治疗作用。然而,Hyp在缺血性脑卒中血管病理生理学中的作用和机制还有待进一步研究。本研究旨在探讨(大电导Ca2+激活的K+)BK通道在Hyp对大鼠脑缺血再灌注(I/R)损伤的血管保护中的作用。在大鼠大脑中动脉闭塞再灌注模型和原代血管平滑肌细胞氧-葡萄糖剥夺/复氧(OGD/R)模型中,对Hyp的浓度梯度进行预处理。检测了一系列指标,包括神经功能缺损评分、梗死体积、丙二醛(MDA)、超氧化物歧化酶(SOD)、脑血流量(CBF)、细胞活力、膜电位以及BK通道α-和β1-亚基的表达。结果表明,Hyp显著减少I/R损伤大鼠的梗死体积,改善神经功能障碍。此外,Hyp可显著逆转I/R诱导的内皮剥脱的脑基底动脉BK通道α-和β1-亚基表达减少的作用。此外,对I/R诱导的MDA增加、SOD降低以及Hyp诱导的CBF的保护作用被iberiotoxin(IbTX)显著逆转。在OGD/R损伤的VSMCs中,Hyp显著逆转下调的细胞活力和BK通道β1-亚基表达。然而,OGD/R和Hyp都不影响BK通道α-亚基的表达,并且Hyp不能诱导VSMCs的超极化。此外,IbTX显著逆转了OGD/R诱导的VSMCs细胞活力和SOD水平降低以及Hyp诱导的MDA产生增加的保护作用。该研究表明,Hyp具有改善血管结果的治疗潜力,其机制与通过上调BK通道抑制氧化应激和改善CBF有关。
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Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and β1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and β1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels β1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

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来源期刊
Neural Plasticity
Neural Plasticity NEUROSCIENCES-
CiteScore
6.80
自引率
0.00%
发文量
77
审稿时长
16 weeks
期刊介绍: Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.
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